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Infect Immun. 2018 Nov 20;86(12). pii: e00709-18. doi: 10.1128/IAI.00709-18. Print 2018 Dec.

Polymorphisms in Receptors Involved in Opsonic and Nonopsonic Phagocytosis, and Correlation with Risk of Infection in Oncohematology Patients.

Author information

1
Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Valladolid, Spain.
2
Servicio de Hematología, Hospital Universitario Río-Hortega, Valladolid, Spain.
3
Servicio de Hematología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
4
Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
5
Departamento de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.
6
Centro de Investigación del Cáncer, Universidad de Salamanca, Salamanca, Spain.
7
Servicio de Microbiología, Hospital Universitario Río-Hortega, Valladolid, Spain.
8
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain.
9
Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Valladolid, Spain mscres@ibgm.uva.es.

Abstract

High-risk hematological malignancies are a privileged setting for infection by opportunistic microbes, with invasive mycosis being one of the most serious complications. Recently, genetic background has emerged as an unanticipated risk factor. For this reason, polymorphisms for genes encoding archetypal receptors involved in the opsonic and nonopsonic clearance of microbes, pentraxin-3 (PTX3) and Dectin-1, respectively, were studied and correlated with the risk of infection. Fungal, bacterial, and viral infections were registered for a group of 198 patients with high-risk hematological malignancies. Polymorphisms for the pentraxin-3 gene (PTX3) showed a significant association with the risk of fungal infection by Candida spp. and, especially, by Aspergillus spp. This link remained even for patients undergoing antifungal prophylaxis, thus demonstrating the clinical relevance of PTX3 in the defense against fungi. CLEC7A polymorphisms did not show any definite correlation with the risk of invasive mycosis, nor did they influence the expression of Dectin-1 isoforms generated by alternative splicing. The PTX3 mRNA expression level was significantly lower in samples from healthy volunteers who showed these polymorphisms, although no differences were observed in the extents of induction elicited by bacterial lipopolysaccharide and heat-killed Candida albicans, thus suggesting that the expression of PTX3 at the start of infection may influence the clinical outcome. PTX3 mRNA expression can be a good biomarker to establish proper antifungal prophylaxis in immunodepressed patients.

KEYWORDS:

Dectin-1; PTX3; SNP; fungal infection; oncohematology

PMID:
30275011
PMCID:
PMC6246897
DOI:
10.1128/IAI.00709-18
[Indexed for MEDLINE]
Free PMC Article

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